IRS2 and IRS1 mediate many of the cellular actions of insulin (INS). Results from model organisms suggest IRS2 is involved in the IGF1/GH1 axis that appears to influence ageing in model organisms. In Drosophila, loss of chico, an insulin receptor substrate, extends lifespan [ 11292874]. IRS2 brain-specific knockout mice were overweight, hyperinsulinemic, glucose intolerant, yet more active and lived up to 18% longer [ 17641201]. In another experiment, however, IRS2 knockout mice were reported to have a shorter median lifespan. Heterozygous animals had normal lifespans [ 17928362]. IRS2 may also be involved in the extended lifespan of other mouse strains [ 11927387]. In humans, mutations in IRS2 have been associated with diabetes [ 11473060]. IRS2 likely plays a role in some human age-related pathologies, but its exact impact on the human ageing process is unknown.

References

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